The principal overall objective of this research is the development of gas-phase analytical techniques for the determination of intact glucuronides in biologic fluids. Human urine and rat bile are used as the main sources of glucuronides. Some standard compounds are obtained commercially to use as markers, internal standards, or for mass spectrometric data collection. The best method for determining drug and estrogen glucuronides in urine has been permethylation of the residue obtained from the evaporation of 100 microliter aliquots. Other isolation and derivatization methods have not been so successful. Packed columns with either OV-17 or SE-30 as the liquid phase have been used to date, and capillary columns are being tested also. The mass spectral properties of all glucuronides observed have been determined. In the future, these techniques will allow us to study glucuronide metabolism in the human, with possible emphasis on genetic control. BIBLIOGRAPHIC REFERENCES: R.M. Thompson. Permethylation of barbiturates. Variation in product ratios with varying methylsulfinymethide carbanion. J. Pharm. Sci., 65, 288-290 (1976). R.M. Thompson. Identification of drugs, drug metabolites and other compounds in urine by permethylation and gas-phase analysis. Res. Commun. Chem. Path. Pharmacol. 16, 145-154 (1977).